Introduction/Background The insulin-like growth factor 1 receptor (IGF1R) plays a key role in regulating growth and invasiveness in epithelial ovarian cancer (EOC), therefore is regarded as a promising therapeutic target. Recently, it has been shown that IGF1 can regulate dendritic cell (DC) maturation and T cell activation. Our study aims to investigate the combination effect of IGF1R inhibition and anti-PD-1 treatment on EOC.

Methodology EOC cell lines were co-cultured with IGF1R inhibitor (AEW-541)-treated-DCs. DC differentiation and EOC proliferation levels were evaluated by Flow Cytometry Assay (FACS). C57BL/6 mice with established peritoneal ovarian cancer were injected with single or combined anti-PD-1 and AEW-541 treatment, and their survival was evaluated. conventional DCs and T-cell population levels were analyzed by FACS. Finally, RNA was extracted from tumors and RNA sequencing was performed.

Results IGF1R inhibitor treatment significantly induced DC differentiation in AEW-541 pre-treated-DCs compared to control after 24 h. In addition, Differentiated AEW-541-treated-DCs significantly decreased EOC cell proliferation. In vivo experiment showed that combined anti-PD-1/IGF1R treatment decreased tumor weight compared to single treatments. Moreover, the anti-PD-1/IGF1R treatment significantly increased the conventional DCs compared to AEW-541 and anti-PD-1 treatments. The Gene Ontology (GO) analysis indicate that the most significant differential biological process terms were immune response by increased lymphocytes cells activation.

Conclusion IGF1R pathway inhibition in differentiated DCs suppressed EOC cell proliferation. IGF1R inhibitor combined with anti-PD-1 may result in enhanced anti-tumor activity. Thus, restoring the anti-tumor immune response by IGF1R targeting in combination with immunotherapy may be an effective therapy for EOC.

Disclosures All authors declare no conflict of interest and no financial benefits from the conducted research .